Methods for delivery of biphasic electrical pulses for non-thermal ablation

Abstract

The present invention provides systems, methods, and devices for electroporation-based therapies (EBTs). Embodiments provide patient-specific treatment protocols derived by the numerical modeling of 3D reconstructions of target tissue from images taken of the tissue, and optionally accounting for one or more of physical constraints or dynamic tissue properties. The present invention further relates to systems, methods, and devices for delivering bipolar electric pulses for irreversible electroporation exhibiting reduced or no damage to tissue typically associated with an EBT-induced excessive charge delivered to the tissue.

The invention claimed is: 
     
       1. A method comprising:
 activating a generator; wherein the generator is configured to deliver at least one burst of electrical pulses to a target area at a frequency of at least 40 kHz; 
 wherein the at least one burst comprises a first burst of at least five electrical pulses each with a pulse length of 10 μs or less, a second burst of at least five electrical pulses each with a pulse length of 10 μs or less, and there is a time delay of at least 1 μs between the first burst and the second burst; 
 wherein at least one of the electrical pulses is configured to alternate polarity or the at least one burst of electrical pulses comprises at least a first electrical pulse having a first polarity and at least a second electrical pulse having a second polarity; and 
 wherein the at least one burst of electrical pulses is sufficient to non-thermally ablate cells of the target area. 
 
     
     
       2. The method of  claim 1 , wherein at least one of the electrical pulses is sufficient to irreversibly electroporate cells of the target area. 
     
     
       3. The method of  claim 1 , wherein the at least five electrical pulses of the first and second bursts have a pulse length of 5-10 μs. 
     
     
       4. The method of  claim 1 , wherein:
 a combined length of the first electrical pulse and the second electrical pulse combined comprises voltage applied for a total of 1 μs to 20 μs; 
 each burst of electrical pulses comprises a voltage applied for a total of 40 μs to 200 μs; 
 and the bursts are delivered at a repetition rate of 60-90 bursts per minute. 
 
     
     
       5. The method of  claim 1 , wherein the first electrical pulse and the second electrical pulse have the same or different length and the same or different amplitude. 
     
     
       6. The method of  claim 1 , wherein there is no delay between the first electrical pulse and the second electrical pulse, or there is a delay between the first electrical pulse and the second electrical pulse of 1 μs to 5 μs in which no energy is delivered. 
     
     
       7. The method of  claim 1 , wherein the at least one burst is configured to result in a zero net charge. 
     
     
       8. The method of  claim 1 , wherein at least one of the electrical pulses comprises a single electrical pulse that alternates polarity. 
     
     
       9. The method of  claim 8 , wherein opposite polarity portions of the single electrical pulse have the same or different length and the same or different amplitude. 
     
     
       10. The method of  claim 8 , wherein positive and negative voltages are the same for opposite polarity portions of the single electrical pulse. 
     
     
       11. The method of  claim 8 , wherein a charge magnitude between a positive polarity and a negative polarity of the single electrical pulse is the same. 
     
     
       12. The method of  claim 1 , further comprising placing a probe near the target area; wherein the probe comprises at least two electrodes. 
     
     
       13. The method of  claim 1 , further comprising placing a probe near the target area; wherein the probe comprises at least a first electrode. 
     
     
       14. The method of  claim 13 , further comprising placing a surface electrode on a patient. 
     
     
       15. A method comprising:
 activating a generator; wherein the generator is configured to deliver at least one burst of electrical pulses to a target area at a frequency of at least 40 kHz; 
 wherein the at least one burst comprises a first burst of at least five electrical pulses each with a pulse length of 10 μs or less, a second burst of at least five electrical pulses each with a pulse length of 10 μs or less, and there is a time delay of up to 1 second between the first burst and the second burst; 
 wherein at least one of the electrical pulses is configured to switch polarity from a positive potential to a negative potential; and 
 wherein at least one of the electrical pulses is sufficient to non-thermally ablate at least a portion of cells of the target area. 
 
     
     
       16. The method of  claim 15 , further comprising placing a probe in the target area; wherein the probe comprises a shaft with at least a first electrode and a second electrode. 
     
     
       17. The method of  claim 16 , wherein the shaft comprises the first electrode and the second electrode spaced 0.1 mm to 5 cm apart from one another. 
     
     
       18. A method comprising:
 activating a generator; wherein the generator is configured to deliver at least one burst of electrical pulses to a target area with a frequency of at least 40 kHz; 
 wherein the at least one burst comprises a first burst of at least five electrical pulses each with a pulse length of 10 μs or less, and a second burst of electrical pulses of at least five electrical pulses each with a pulse length of 10 μs or less, and there is a time delay of up to 1 second between the first burst and the second burst; 
 wherein polarity of a plurality of the electrical pulses is configured to alternate between a positive potential and a negative potential or configured to alternate between a negative potential and a positive potential between the electrical pulses; and 
 wherein the plurality of electrical pulses are sufficient to non-thermally ablate cells of the target area. 
 
     
     
       19. The method of  claim 18 , wherein the at least five electrical pulses of the first and second bursts have a pulse length of 5-10 μs. 
     
     
       20. The method of  claim 19 , wherein there is a time delay of 1 μs between each electrical pulse of the at least five electrical pulses of the first burst. 
     
     
       21. The method of  claim 18 , wherein the at least five electrical pulses of the first and second bursts have a pulse length of 10 μs. 
     
     
       22. The method of  claim 21 , wherein there is a time delay of 1 μs between each electrical pulse of the at least five electrical pulses of the first burst. 
     
     
       23. The method of  claim 18 , further comprising placing a probe in the target area; wherein the probe comprises at least two electrodes. 
     
     
       24. The method of  claim 23 , wherein the probe is flexible.